1. Field of the Invention
The present invention relates to a fine-particulate, water-insoluble medicine, and a complex of the same with a polymer electrolyte. More particularly, the present invention is related to a medicine in the form of ultrafine particles obtained by irradiating a laser beam onto particles, and an ultrafine particle-polymer electrolyte complex.
2. Description of Related Art
Medicines insoluble to solvents, such as anticancer drugs, are insoluble to water and are hardly absorbed by cells, so that the bioavailability thereof is low. Therefore, when these water-insoluble medicines are used for injection, a solubilizer is often added for the purpose of enhancing the water solubility of the medicines to thereby improve the bioavailability thereof. However, this solubilizer has toxicity problems.
For improving the intake of the water-insoluble medical drugs by cells without using a solubilizer, the size of the drugs can be reduced to ultrafine particles which can pass through the cell membrane of the affected part. The size of ultrafine particles which can pass through a cell membrane is considered to be 200 nm or less.
As an organic substance is expected to exhibit interesting improvement and changes in properties by size-reduction, various methods for forming ultrafine particles of an organic compound have been proposed. For example, a method has been disclosed in which an organic compound dispersed in a solvent is irradiated with a laser beam to thereby form ultrafine particles of the organic compound (for example, see Japanese Unexamined Patent Application, First Publication No. 2001-113159). In the method disclosed in Japanese Unexamined Patent Application, First Publication No. 2001-113159, an organic compound is irradiated with a beam having a wavelength within the absorption band wavelength, so that thermal stress cracking is caused by linear optical absorption at a relatively weak chemical bond within the molecular structure, thereby forming ultrafine particles. However, simultaneously with the formation of ultrafine particles, it is highly possible that electronic excitation occurs in some portions of the organic compound to cause a photochemical reaction, such that the organic compound decomposes. Especially when the organic compound is a medical drug to be administered into a body, there is a danger that the decomposition product may harmfully affect the body, and hence, such a serious situation must be avoided.
For improving the method disclosed in Japanese Unexamined Patent Application, First Publication No. 2001-113159, a method for forming ultrafine particles has been proposed in which the organic compound within the liquid to be treated is irradiated with a laser beam having a wavelength longer than the absorption band (for example, see Japanese Unexamined Patent Application, First Publication No. 2004-267918). Further, a method for forming ultrafine particles has been proposed in which a bulk crystal of an organic compound dispersed in a poor solvent is irradiated with a very short pulsed laser to induce ablation by non-linear absorption, thereby pulverizing the bulk crystal (for example, see Japanese Unexamined Patent Application, First Publication No. 2005-238342).
In these methods, crude particles of an organic compound dispersed in a solvent within a transparent vessel are externally irradiated with a laser beam having a wavelength longer than the absorption band or a very short pulsed laser, thereby pulverizing the organic compound within the solvent. These methods enable formation of ultrafine particles of an organic compound under relatively mild conditions, as compared to the method in which a beam having a wavelength within the absorption band is linearly absorbed. Therefore, in these methods, there is less danger of the organic compound decomposing, and these methods were considered to be suitable for formation of ultrafine particles of insoluble organic compounds in small amounts, especially medical drugs.
However, although the principle of pulverization by laser beam irradiation is assumed to be thermal stress cracking caused by short-term heating by pulse energy, the laser energy absorption properties of the drug and setting of the laser irradiation period become important parameters for forming ultrafine particles of the drug without causing deterioration. In a batchwise method, a laser beam is irradiated onto the drug in a state where the drug is dispersed in solvent within a vessel, or in a state where the drug is being stirred in the vessel. Therefore, in a batchwise manner, it was difficult to control various conditions, such as setting the laser beam irradiation period and uniformly irradiating the laser beam onto the dispersed particles. For example, certain particles are irradiated with the laser beam many times, whereas other particles are not irradiated at all. Therefore, formation of ultrafine particles of a drug which have a uniform particle size within a predetermined range and which are free from deterioration so as to exhibit high bioavailability, has not been achieved at an industrial scale.